Journal of neurotrauma
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Journal of neurotrauma · Aug 2018
Transactive response DNA-binding protein 43 (TDP-43) abnormalities after traumatic brain injury.
Initial studies have found some evidence for transactive response DNA-binding protein 43 (TDP-43) abnormalities after traumatic brain injury (TBI), and the presence of protein inclusions consisting of TDP-43 are a pathological hallmark of amyotrophic lateral sclerosis (ALS), a condition associated with TBI. However, no study has characterized changes in TDP-43 phosphorylation, mislocalization, and fragmentation (i.e., abnormalities linked to hallmark TDP-43 pathology) after TBI, and how these relate to functional outcomes. Further, how TBI affects an individual with a known predisposition to TDP-43 pathology is unknown. ⋯ In the human TBI patients, the only significant finding was increased nuclear accumulation of phosphorylated TDP-43 fragments. The discrepancy between the robust mouse findings and the largely non-significant human findings may be due to factors including heterogeneity in clinical TBI, the small group sizes, and temporal complexities with TDP-43 abnormalities. These findings indicate that TBI can induce a number of TDP-43 abnormalities that may contribute to the neurological consequences of TBI, though further research is still needed.
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Journal of neurotrauma · Aug 2018
Preinjury Migraine History as a Risk Factor for Prolonged Return to School and Sports following Concussion.
Having a preexisting migraine disorder might be a risk factor for a prolonged recovery following a sport-related concussion. We examined whether having a migraine history was associated with a prolonged return to academics and athletics following a concussion. High school and collegiate athletes (n = 1265; 42% female) who sustained a sport-related concussion were monitored by athletic trainers using a web-based surveillance system that collects information about concussion recovery. ⋯ Stratifying the analyses by sex showed that this effect was significant in girls and women with preexisting migraines, but not boys and men with preexisting migraines. There were no group differences in recovery rates when examining return to athletics. Athletes with a preinjury migraine history may be at an elevated risk for a protracted return to school after concussion, especially girls and women.
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Journal of neurotrauma · Aug 2018
Safety and Efficacy of Rose Bengal Derivatives for Glial Scar Ablation in Chronic Spinal Cord Injury.
There are no effective therapies available currently to ameliorate loss of function for patients with spinal cord injuries (SCIs). In addition, proposed treatments that demonstrated functional recovery in animal models of acute SCI have failed almost invariably when applied to chronic injury models. Glial scar formation in chronic injury is a likely contributor to limitation on regeneration. ⋯ RB3 was not taken up by the cells, likely because of its size, and therefore had no effect. Treatment with RB1 also resulted in an increase in serotonin eight days post-treatment in chronically injured spinal cords. Thus, we suggest that unmodified rose Bengal is a potent candidate agent for the development of a therapeutic strategy for scar ablation in chronic SCI.
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Journal of neurotrauma · Aug 2018
Integration of Transplanted Neural Precursors with the Injured Cervical Spinal Cord.
Cervical spinal cord injuries (SCI) result in devastating functional consequences, including respiratory dysfunction. This is largely attributed to the disruption of phrenic pathways, which control the diaphragm. Recent work has identified spinal interneurons as possible contributors to respiratory neuroplasticity. ⋯ Despite the consistent presence of cholinergic interneurons within donor tissue, transneuronal tracing revealed minimal connectivity with host phrenic circuitry. Phrenic nerve recordings revealed changes in burst amplitude after application of a glutamatergic, but not serotonergic antagonist to the transplant, suggesting a degree of functional connectivity between donor neurons and host phrenic circuitry that is regulated by glutamatergic input. Importantly, however, anatomical and functional results were variable across animals, and future studies will explore ways to refine donor cell populations and entrain consistent connectivity.
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Journal of neurotrauma · Aug 2018
Observational StudyPersons with Chronic Spinal Cord Injury Have Decreased Natural Killer Cell and Increased Toll-Like Receptor/Inflammatory Gene Expression.
Infections are the leading cause of death for individuals with traumatic spinal cord injury (SCI). Along with increased infection rates, inflammation is often also observed in persons with chronic SCI. Together, immunological changes post-SCI are also poised to impede neurological recovery and mediate common medical consequences of SCI, including atherogenesis and neuropathic pain. ⋯ We identified 1815 differentially expressed genes in all SCI participants and 2226 differentially expressed genes in persons with SCI rostral to thoracic level 5, compared to uninjured participants. This included marked downregulation of natural killer cell genes and upregulation of the proinflammatory Toll-like receptor signaling pathway. These data provide novel mechanistic insights into the causes underlying the symptoms of immune dysfunction in individuals living with SCI.